Abstract Over the last two decades, we and others have documented the chronic and often debilitating experience of ovarian cancer survivorship which may include poor health related quality of life (HRQOL), elevated anxiety and depression, poor sleep, fatigue, multiple symptoms/side effects, existential concerns, and a generally poor prognosis. Because of compromises to many aspects of HRQOL combined with low rates of survival for the majority of these patients, development of innovative approaches for improving HRQOL and potentially improving clinical outcomes is of paramount importance. This need is particularly true in rural settings where women may have less access to clinic-based support systems. Despite the multiple challenges experienced by ovarian cancer survivors, research targeting the potential efficacy of psychosocial interventions in enhancing HRQOL has been extremely limited. Over the last several years this research team has developed and piloted a web-based group conferencing intervention entitled Living Well (Web-Enhanced Lessons for Living) targeting key concerns of ovarian cancer survivors and developed with input from survivors. The overarching goal of the present submission is to examine the efficacy of the Living Well intervention vs. a Health Promotion active control intervention in a randomized controlled trial in 256 ovarian cancer survivors who have completed primary treatment and are less than 5-years post-diagnosis. We hypothesize that the Living Well Intervention will be efficacious in improving HRQOL, decreasing perceived stress (primary outcomes) and in decreasing depressive mood, anxiety, and fatigue (secondary outcomes). This application is highly innovative because it combines elements of evidence-based psychosocial interventions in a novel way to target the needs of ovarian cancer survivors, using a state-of-the-art web and video conferencing platform that allows wide dissemination, including to rural survivors. This work is highly translational as it is a direct application of findings from mechanistic stress-related research to testing an intervention to reduce stress in ovarian cancer survivors. The significance of the application is that this intervention has the potential to overcome prior barriers to the implementation of such psychosocial interventions and improve HRQOL, thus providing public health benefits to an understudied and compromised cancer population with a high likelihood of recurrence.